Astrocytes, the most abundant glial population in the human central nervous system, normally play critical roles in neuroprotection, immunity, and homeostasis. However, upon exposure to specific neuroinflammatory cues, astrocytes assume a pro-inflammatory, neurotoxic phenotype. Neurotoxic astrocytes promote chronic neuroinflammation, a common driver of many neurodegenerative diseases. Thus, identifying and targeting the signaling pathways that lead to the formation of neurotoxic astrocytes can provide novel therapeutic approaches to curb neurodegeneration. The preclinical development of new drugs targeting neurotoxic astrocytes requires scalable, robust and reproducible assays that harness accurate, translational and accessible in vitro models of the neurotoxic phenotype.

Here, we aimed to

i. Further validate our previously established model of neurotoxic reactive astrocytes through lipidomic profiling

ii. Generate proof-of-concept data demonstrating astrocyte-induced neurotoxic effects in human neurons that can be rescued by an anti-inflammatory agent.